The principal projects to be studied in the next grant period encompass surface-mediated defense reactions and the nature of antihemophilic factor (AHF, factor VIII). The question of whether activation of Hageman factor (HF, factor XII) necessarily requires its enzymatic scission will be reexamined. The amidolytic properties of HF and its carboxy-terminal fragment (HFf), their inhibition by kaolin and other agents and the countervailing effect of HMW kininogen will be examined. Components of surface-mediated reactions will be studied in women taking oral contraceptives, and their relation to activation of plasminogen. Other aspects of plasmin- and non-plasmin-induced fibrinolysis will be studied, as well as modulators of tissue activators of plasminogen, and the site of synthesis of plasminogen. The role of HF in inflammatory states will be examined in animals. The pathogenesis of circulating anticoagulants against antihemophilic factor (AHF, factor VIII) will be examined in vitro. The site of storage of procoagulant AHF, and the nature of the AHF molecule in normal individuals and those with mild hemophilia will be investigated. Other studies will encompass examination of the hemostatic defects of unusual patients, enzyme-labelled assays for AHF, and the anticoagulant properties of chlorazol fast pink.